Biosynthetic potentials of metabolites and their hierarchical organization.

Matthäus F, Salazar C, Ebenhöh O - PLoS Comput. Biol. (2008)

Bottom Line:
We observe that most of the resulting consensus scopes overlap or are fully contained in others, revealing a hierarchical ordering of metabolites according to their biosynthetic potential.A central result is that chemically very similar substances with different biological functions may differ significantly in their biosynthetic potentials.Our studies provide an important step towards understanding fundamental design principles of metabolic networks determined by the structural and functional complexity of metabolites.

ABSTRACTA major challenge in systems biology is to understand how complex and highly connected metabolic networks are organized. The structure of these networks is investigated here by identifying sets of metabolites that have a similar biosynthetic potential. We measure the biosynthetic potential of a particular compound by determining all metabolites than can be produced from it and, following a terminology introduced previously, call this set the scope of the compound. To identify groups of compounds with similar scopes, we apply a hierarchical clustering method. We find that compounds within the same cluster often display similar chemical structures and appear in the same metabolic pathway. For each cluster we define a consensus scope by determining a set of metabolites that is most similar to all scopes within the cluster. This allows for a generalization from scopes of single compounds to scopes of a chemical family. We observe that most of the resulting consensus scopes overlap or are fully contained in others, revealing a hierarchical ordering of metabolites according to their biosynthetic potential. Our investigations show that this hierarchy is not only determined by the chemical complexity of the metabolites, but also strongly by their biological function. As a general tendency, metabolites which are necessary for essential cellular processes exhibit a larger biosynthetic potential than those involved in secondary metabolism. A central result is that chemically very similar substances with different biological functions may differ significantly in their biosynthetic potentials. Our studies provide an important step towards understanding fundamental design principles of metabolic networks determined by the structural and functional complexity of metabolites.

pcbi-1000049-g001: Consensus scope overlap for the 13 clusters obtained with the hierarchical clustering method.Two of the consensus scopes (VII, XI) are mutually disjoint, while others overlap (e.g., III and IX), and some consensus scopes are fully contained in others (e.g., VI in III).

Mentions:
The extreme variation in consensus scope sizes raises the question whether they may be ordered by increasing biosynthetic potential. In fact, some consensus scopes are contained in others, some are mutually disjoint and others partially overlap. We schematically visualize the pairwise overlaps in Figure 1. The figure shows that the immensely complex metabolic network displays an intricate hierarchical organization with respect to the biosynthetic potentials of the participating compounds. In the following, we will analyze similarities and differences in the chemical structure of metabolites belonging to the same cluster and particularly address the question whether the identified hierarchy may be explained by chemical structure alone or whether the biological role of metabolites or clusters of metabolites is also reflected in the metabolic organization.

pcbi-1000049-g001: Consensus scope overlap for the 13 clusters obtained with the hierarchical clustering method.Two of the consensus scopes (VII, XI) are mutually disjoint, while others overlap (e.g., III and IX), and some consensus scopes are fully contained in others (e.g., VI in III).

Mentions:
The extreme variation in consensus scope sizes raises the question whether they may be ordered by increasing biosynthetic potential. In fact, some consensus scopes are contained in others, some are mutually disjoint and others partially overlap. We schematically visualize the pairwise overlaps in Figure 1. The figure shows that the immensely complex metabolic network displays an intricate hierarchical organization with respect to the biosynthetic potentials of the participating compounds. In the following, we will analyze similarities and differences in the chemical structure of metabolites belonging to the same cluster and particularly address the question whether the identified hierarchy may be explained by chemical structure alone or whether the biological role of metabolites or clusters of metabolites is also reflected in the metabolic organization.

Bottom Line:
We observe that most of the resulting consensus scopes overlap or are fully contained in others, revealing a hierarchical ordering of metabolites according to their biosynthetic potential.A central result is that chemically very similar substances with different biological functions may differ significantly in their biosynthetic potentials.Our studies provide an important step towards understanding fundamental design principles of metabolic networks determined by the structural and functional complexity of metabolites.

ABSTRACTA major challenge in systems biology is to understand how complex and highly connected metabolic networks are organized. The structure of these networks is investigated here by identifying sets of metabolites that have a similar biosynthetic potential. We measure the biosynthetic potential of a particular compound by determining all metabolites than can be produced from it and, following a terminology introduced previously, call this set the scope of the compound. To identify groups of compounds with similar scopes, we apply a hierarchical clustering method. We find that compounds within the same cluster often display similar chemical structures and appear in the same metabolic pathway. For each cluster we define a consensus scope by determining a set of metabolites that is most similar to all scopes within the cluster. This allows for a generalization from scopes of single compounds to scopes of a chemical family. We observe that most of the resulting consensus scopes overlap or are fully contained in others, revealing a hierarchical ordering of metabolites according to their biosynthetic potential. Our investigations show that this hierarchy is not only determined by the chemical complexity of the metabolites, but also strongly by their biological function. As a general tendency, metabolites which are necessary for essential cellular processes exhibit a larger biosynthetic potential than those involved in secondary metabolism. A central result is that chemically very similar substances with different biological functions may differ significantly in their biosynthetic potentials. Our studies provide an important step towards understanding fundamental design principles of metabolic networks determined by the structural and functional complexity of metabolites.